The development of microcantilever force sensors has enabled development of instrumentation such as atomic force microscope (AFM) tools, which have further led to the development of cantilever based sensing. However, at microscale dimensions, there are limits with respect to the level of frequency achievable and the level of sensitivity attainable. In this regard, the standard approaches used to make microelectromechanical systems (MEMS) provide little access to the nanoscale, where large improvement in sensitivity can be attained.
Cells exert forces on their surroundings using their cytoskeleton. The cytoskeleton is a very complex and dynamic structure which is directly coupled to all organelles within a cell and many, if not all, signaling networks within a cell (Janmey, P. A., Physiological Reviews 87 (1998) 763-781). Thus, monitoring the state of a cell's cytoskeleton is a promising approach for performing phenotypic screening of potential pharmaceutical reagents for both desired and undesired activity within a cell.
The ability to measure forces exerted by biological specimen have encountered significant limitations. To overcome this limitation, prior work has been focusing on optical measurement techniques. However, such technique is often limited by the resolution attainable. Additionally, some prior efforts of delivery and control systems fail to maintain the viability of the biological sample under study, while providing a mechanism to extract signals from a force sensor to a computer for readout and analysis.
Tissue constructs have been used to perform phenotypic screening of pharmaceutical by monitoring the contraction of large populations of cells. However, results from tissue construct often are low in resolution, and thus subtle effects may be missed. Another drawback of tissue constructs is that they are slow to form and grow. Tissue constructs can also demand relatively large quantities of reagents and are not amenable to large scale integration/automation nor to simultaneous fluorescent microscopy.
Thus, a need exists for an improved force sensor system to provide better monitoring and measuring techniques of biological cells.